Serra Magda F, Cotias Amanda C, Pimentel Andreza S, Arantes Ana Carolina S de, Pires Ana Lucia A, Lanzetti Manuella, Hickmann Jandir M, Barreto Emiliano, Carvalho Vinicius F, Silva Patrícia M R E, Cordeiro Renato S B, Martins Marco Aurélio
Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil.
Institute of Biomedical Science, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil.
Antioxidants (Basel). 2022 Aug 26;11(9):1659. doi: 10.3390/antiox11091659.
Gold nanoparticles (AuNPs) can inhibit pivotal pathological changes in experimental asthma, but their effect on steroid-insensitive asthma is unclear. The current study assessed the effectiveness of nebulized AuNPs in a murine model of glucocorticoid (GC)-resistant asthma.
A/J mice were sensitized and subjected to intranasal instillations of ovalbumin (OVA) once a week for nine weeks. Two weeks after starting allergen stimulations, mice were subjected to Budesonide or AuNP nebulization 1 h before stimuli. Analyses were carried out 24 h after the last provocation.
We found that mice challenged with OVA had airway hyperreactivity, eosinophil, and neutrophil infiltrates in the lung, concomitantly with peribronchiolar fibrosis, mucus production, and pro-inflammatory cytokine generation compared to sham-challenged mice. These changes were inhibited in mice treated with AuNPs, but not Budesonide. In the GC-resistant asthmatic mice, oxidative stress was established, marked by a reduction in nuclear factor erythroid 2-related factor 2 (NRF2) levels and catalase activity, accompanied by elevated values of thiobarbituric acid reactive substances (TBARS), phosphoinositide 3-kinases δ (PI3Kδ) expression, as well as a reduction in the nuclear expression of histone deacetylase 2 (HDAC2) in the lung tissue, all of which sensitive to AuNPs but not Budesonide treatment.
These findings suggest that AuNPs can improve GC-insensitive asthma by preserving HDAC2 and NRF2.
金纳米颗粒（AuNPs）可抑制实验性哮喘的关键病理变化，但其对激素不敏感型哮喘的影响尚不清楚。本研究评估了雾化吸入AuNPs在糖皮质激素（GC）抵抗性哮喘小鼠模型中的有效性。
对A/J小鼠进行致敏，每周经鼻内滴注一次卵清蛋白（OVA），共9周。在开始过敏原刺激两周后，在刺激前1小时对小鼠进行布地奈德或AuNP雾化。在最后一次激发后24小时进行分析。
我们发现，与假激发小鼠相比，用OVA激发的小鼠出现气道高反应性、肺内嗜酸性粒细胞和中性粒细胞浸润，同时伴有细支气管周围纤维化、黏液分泌和促炎细胞因子生成。这些变化在用AuNPs治疗的小鼠中受到抑制，但用布地奈德治疗的小鼠则没有。在GC抵抗性哮喘小鼠中，建立了氧化应激，其特征是核因子红细胞2相关因子2（NRF2）水平和过氧化氢酶活性降低，同时肺组织中硫代巴比妥酸反应性物质（TBARS）、磷酸肌醇3激酶δ（PI3Kδ）表达升高，以及组蛋白去乙酰化酶2（HDAC2）核表达降低，所有这些对AuNPs治疗敏感，但对布地奈德治疗不敏感。
这些发现表明，AuNPs可通过保留HDAC2和NRF2来改善GC不敏感型哮喘。
